Acetylation Is Crucial for p53-Mediated Ferroptosis and Tumor Suppression.

ABSTRACT: Although previous studies indicate that loss of p53-mediated cell cycle arrest, apoptosis, and senescence does not completely abrogate its tumor suppression function, it is unclear how the remaining activities of p53 are regulated. Here, we have identified an acetylation site at lysine K98 in mouse p53 (or K101 for human p53). Whereas the loss of K98 acetylation (p53^K98R) alone has very modest effects on p53-mediated transactivation, simultaneous mutations at all four acetylation sites (p53^4KR: K98R+ 3KR[K117R+K161R+K162R]) completely abolish its ability to regulate metabolic targets, such as TIGAR and SLC7A11. Notably, in contrast to p53^3KR, p53^4KR is severely defective in suppressing tumor growth in mouse xenograft models. Moreover, p53^4KR

SUBMITTER: Wang SJ 

PROVIDER: S-EPMC5227654 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature